title: Dose constraint for minimizing grade 2 rectal bleeding following brachytherapy combined with external beam radiotherapy for localized prostate cancer: rectal dose-volume histogram analysis of 457 patients.
abstract: OBJECTIVE
  To determine the rectal tolerance to Grade 2 rectal bleeding after I-125 seed brachytherapy combined with external beam radiotherapy (EBRT), based on the rectal dose-volume histogram.
  
  
  METHODS
  A total of 458 consecutive patients with stages T1 to T3 prostate cancer received combined modality treatment consisting of I-125 seed implantation followed by EBRT to the prostate and seminal vesicles. The prescribed doses of brachytherapy and EBRT were 100 Gy and 45 Gy in 25 fractions, respectively. The rectal dosimetric factors were analyzed for rectal volumes receiving >100 Gy and >150 Gy (R100 and R150) during brachytherapy and for rectal volumes receiving >30 Gy to 40 Gy (V30-V40) during EBRT therapy in 373 patients for whom datasets were available. The patients were followed from 21 to 72 months (median, 45 months) after the I-125 seed implantation.
  
  
  RESULTS
  Forty-four patients (9.7%) developed Grade 2 rectal bleeding. On multivariate analysis, age (p = 0.014), R100 (p = 0.002), and V30 (p = 0.001) were identified as risk factors for Grade 2 rectal bleeding. The rectal bleeding rate increased as the R100 increased: 5.0% (2/40 patients) for 0 ml; 7.5% (20/267 patients) for >0 to 0.5 ml; 11.0% (11/100 patients) for >0.5 to 1 ml; 17.9% (5/28 patients) for >1 to 1.5 ml; and 27.3% (6/22 patients) for >1.5 ml (p = 0.014). Grade 2 rectal bleeding developed in 6.4% (12/188) of patients with a V30 ≤35% and in 14.1% (26/185) of patients with a V30 >35% (p = 0.02). When these dose-volume parameters were considered in combination, the Grade 2 rectal bleeding rate was 4.2% (5/120 patients) for a R100 ≤0.5 ml and a V30 ≤35%, whereas it was 22.4% (13/58 patients) for R100 of >0.5 ml and V30 of >35%.
  
  
  CONCLUSIONS
  The risk of rectal bleeding was found to be significantly volume-dependent in patients with prostate cancer who received combined modality treatment. Rectal dose-volume analysis is a practical method for predicting the risk of development of Grade 2 rectal bleeding.
authors.affiliation: Department of Radiology, Tokyo Medical Center, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shiraishi
authors.forename: Atsunori
authors.initials: A
authors.lastname: Yorozu
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohashi
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Toya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Seki
authors.forename: Kayo
authors.initials: K
authors.lastname: Yoshida
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kaneda
authors.forename: Shiro
authors.initials: S
authors.lastname: Saito
authors.forename: Toru
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Hanada
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Shigematsu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D001918:Brachytherapy / Q000009:adverse effects* / Q000379:methods; D017024:Chemotherapy, Adjuvant / Q000379:methods; D019583:Dose Fractionation, Radiation; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000209:etiology*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D058958:Organs at Risk / Q000528:radiation effects*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000150:complications*; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D012007:Rectum / Q000528:radiation effects*
chemical_list: D000726:Androgen Antagonists; D007457:Iodine Radioisotopes